We report on a one-step assembly route where supported lipid bilayers (SLB) are deposited on functionalized colloidal mesoporous silica (CMS) nanoparticles, resulting in a core−shell hybrid system (SLB@CMS). The supported membrane acts as an intact barrier against the escape of encapsulated dye molecules. These stable SLB@CMS particles loaded with the anticancer drug colchicine are readily taken up by cells and lead to the depolymerization of microtubules with remarkably enhanced efficiency as compared to the same dose of drug in solution.